1. Field of the Invention
This invention relates to a new compound, more particularly, to a compound for inhibiting growths of cancer cells and promoting apoptosis of the cancer cells.
2. Description of Related Art
Lung cancer has become one of the leading causes of cancer-related morbidity and mortality in the world. According to statistics, lung cancer is the most common cause of death of cancer in Taiwan. Lung cancer can be mainly divided into a small cell lung carcinoma (hereinafter referred to SCLC) and a non-small cell lung carcinoma (hereinafter referred to NSCLC). Among these, NSCLC takes about 80% of the lung cancer cases and SCLC takes about 20%. Most of the NSCLC patients were observed an overexpression of epidermal growth factor receptor (hereinafter referred to EGFR). Therefore, EGFR which has a mutation with abnormal overexpression becomes one of the target proteins for new drugs.
Irresa, also known as Gefitinib or ZD1839, is a small molecule tyrosine kinase inhibitor (TKI) and has been approved for clinical treatment of NSCLC. Irresa competes with the binding of ATP to the substrate binding site of the intracellular tyrosine kinase domain of EGFR; thereby inhibit tyrosine kinase autophosphorylation and block downstream signal transduction.
The anticancer activities of Irresa are related to the mutation of EGFR. For example, the deletions in exon 19 and the substitution of an arginine for leucine at codon 858 (L858R) in exon 21 are the most common EGFR activating mutations, which increase the sensitivity of Irresa in tumors. The resistances of Irresa in lung cancer therapy have been reported in several studies and the other secondary EGFR mutations have been found to associate with acquired resistance. Based on clinical data, about 50% of NSCLC patients having resistances to Irresa have a mutation at position 790 of the amino acid sequence of EGFR, T790M (from a threonine to a methionine). T790M mutation is located in the ATP-binding site of EGFR structure and blocks EGFR-TKI binding. Moreover, T790M also can increase the affinity of ATP binding to the cleft to enhance the activity of EGFR.
Formula (I) and a salt thereof,
wherein, m is an integer of 2 to 7, and R is independently at least one selected from the group consisting of hydrogen and C1-C20 alkyl.
In an embodiment of the present invention, m is 2 and R is C1-C13 alkyl.
In an embodiment of the present invention, m is 2 and R is C12 alkyl.
In an embodiment of the present invention, the compound of the present invention is used to promote an apoptosis in cancer cell and inhibit a growth of the cancer cell. Preferably, the cancer cell is at least one selected from the group consisting of lung cancer cell, rectal cancer cell and bladder cancer cell.
In an embodiment of the present invention, the compound of Formula (I) of the present invention is used to suppress an activity of epidermal growth factor receptor (hereinafter referred to EGFR) protein kinase, so as to promote an apoptosis in the cancer cell.
This invention further provides a pharmaceutical composition comprising the compound of Formula (I) or a salt thereof and a pharmaceutically acceptable carrier.
This invention further provides a method for treating a cancer in a subject, comprising a step of administrating an effective amount of the pharmaceutical composition of the present invention to the subject wherein the cancer is at least one selected from the group consisting of lung cancer, rectal cancer and bladder cancer.